The National Alzheimer's Prevention Act, signed into law one year ago, calls for a national strategy for defeating this terrible disease. A late-stage draft of the strategy sets a goal to develop a cure by the year 2025. While many have suggested a timeline with more urgency, say by 2020, others have suggested that this timeline is too ambitious.

On the one hand, given our still poor understanding of the disease, coupled with a dismal track record of success for pipeline drugs over the past decade, it seems unlikely that a cure could be developed prior to 2025. In fact, against the backrop of recent evidence, it may well take longer than that.

On the other hand, we could stop short of a cure and still have great success. For example, many chronic diseases like diabetes and hypertension have no cure, but we have effective treatments, and we manage those diseases with high efficacy. It is likely that new drugs, developed well before 2025, will give us greater treatment benefits for patients with Alzheimer's.

Perhaps of greater importance is the fact that we already have approved therapies that can significantly slow Alzheimer's disease progression. However, since we commonly detect the disease too late and intervene only after massive brain damage has occurred, the perception among physicians is that treatment is unhelpful. This nihilistic perception actually perpetuates the cycle of late intervention because, believing that there is no treatment, many MDs don't look for early signs Alzheimer's.

In this regard, a key element to an effective national Alzheimer's strategy would be to update physicians about the benefits of early detection and equip them with the tools and training to proactively monitor the cognitive health of their patients. When a cure is developed, that will be great. But in the meantime, we can find the disease early and treat it as effectively as possible with robust therapy (drugs, diet, physical exercise, control of diabetes and hypertension, intellectual stimulation, social engagement, and caregiver education). Such a comprehensive approach has been shown to significantly delay disease progression in a meaningful percentage of early-stage patients.

MCI is a subtle loss of thinking ability, such as impaired memory or judgment, that is not severe enough to interfere with the person's normal activities of living. The study showed about a 20% incidence rate which is squarely in line with previous estimates.

The press has been largely focused on the fact that, in this study, men between the ages of 70 and 89 years had a higher incidence of MCI than women of the same age. This is probably true. It is also probably easy to explain.

MCI is not a disease, it is merely a descriptor term for a certain level of cognitive impairment. It refers to the degree of impairment that falls between normal cognition and the severe loss of function that we call dementia. Asking "why" a person has MCI is a whole different question with a host of common answers including depression, thyroid disease, stroke, sleep disorder, Alzheimer's disease, and anxiety, to name just a few.

The question of "why" a person has MCI was not adressed in this study, but may shed some important light on the observed gender differences. For example, sleep disorders and certain cardiovascular conditions, like hypertension and stroke, are common causes of MCI and are somewhat more prevalent among men than women. Clearly, conditions that impair memory and are also more common in men, could fully explain the observed gender differences in this study. In that respect, these results are hardly surprising and, in fact, make perfect sense.

It would be truly worthy of a media frenzy if researchers controlled for each cause of MCI and still found that one gender was more susceptible than the other. But despite many misleading headlines, that was not the case in this study.

As genetic testing has become more commonplace in medicine, we have all seen frequent examples of overstatement, where writers and speakers confuse "higher risk" with "absolute certainty". This has been an especially maddening component of arguments against testing for the APOe4 gene associated with increased risk for Alzheimer's disease.

A great many of these faulty arguments state that learning about a genetic risk for an incurable disease is pointless. (I have refuted that argument many times but that is not the point of this post). This week, research published in Archives of Neurology strengthens the case for genetic testing.

In a study from the University of Washington in St. Louis, more than 200 participants aged 45 to 88 reported on their physical exercise habits and submitted to spinal fluid measures or PET scans to determine the amount of accumulated amyloid protein in their brains. They also had their APOe4 status checked and researchers found that, among those who carried the APOe4 gene, regular exercisers had less amyloid load than sedentary members of the group. Interestingly, this was not the case among the APOe4 non-carriers.

This was a small study and needs replication before we can conclude that physical exercise staves off amyloid accumulation in those with genetic risks for AD. However, the study has a very intuitive finding and gives credence to a much larger body of work showing that good cardiovascular health may reduce the risk of Alzheimer's disease.

The suggestion from this study is very significant. It could be that genetic risk for AD (usually considered to be an unmodifiable risk), could possibly be reduced by physical exercise. If so, it will put a whole new spin on those old arguments against genetic testing.

As we noted here late last year, there are several promising new Alzheimer's treatments in the FDA pipeline. While the early stages of the pipeline are predictably more full than the later stages, we expect to see data this year on at least two agents that are nearing the end of the trial process.

Earlier this week, Baxter announced the successful conclusion of their futility analysis on IVIG for treating symptoms in mild to moderate stage Alzheimer's patients. The futility analysis, conducted by the Data Safety and Monitoring Board (DSMB), indicated that further trial efforts could proceed with no modification to the protocol. With that result, Baxter immediately announced plans to initiate a confirmatory Phase III trial to begin in early 2012.

IVIG, or intravenous immunoglobulin, has been marketed for some 25 years to treat autoimmune diseases, but has not previously been studied and approved for treating Alzheimer's disease. Given it's historical safety profile and early data indicating efficacy in Alzheimer's patients, it may be the next drug approved in this field.

Cognition, or thinking ability, is a complex concept and is difficult to measure. Nonetheless, many studies have shown that intellectual activity seems to be correlated with some measure of"better cognition". This makes intuitive sense and has given rise to many "use it or lose it" type slogans aimed at our aging population.

In a study published online today in the Archives of Neurology, researchers from Berkeley's Neuroscience Institute found that, seniors who pursued intellectual hobbies throughout their lives, accumulated less amyloid plaque in their brains later in life. This is interesting in a couple of ways.

First, while cognition can be difficult to measure, accumulated amyloid plaque in the brain has become increasingly easier to measure with new agents that bind to amyloid and "light up" during a PET scan of the brain. We can now get a fairly accurate read of amyloid load which is, by all accounts, much more tangible than our best measures of cognition.

An important caveat to this point is that, while we can accurately measure the amount of amyloid in the brain, we are still somewhat unclear on what that means. For sure, amyloid accumulation is neurotoxic (harmful to brain cells), but such accumulation may be a reaction to some other disease process that would be even more damaging without the presence of amyloid plaques. This is a topic of intense, ongoing study.

The second interesting take-away from this new research is that the subjets reported a lifetime of intellectual activity. If this work is repeated in larger studies and deemed to be conclusive, it will not mean that playing bridge and studying music in retirement will keep amyloid plaques out of the brain. It may be that an entire lifetime of brain exercise is the minimum threshold for a meaningful benefit.

In any case, it is very encouraging to see pathological evidence supporting the theory that brain exercise can have cognitive benefits during our elder years. We will watch ongoing research in this area with great interest.

I am encouraged by the top-level recognition of Alzheimer's as a major social problem, and by the seeming seriousness of the current administration to tackle it. However, the lack of funding in these fiscally challenging times is concerning. For perspective, we commit more than $6B annually in federal funds to cancer research compared to about a half a billion for AD research. Current lobbying efforts are aiming for a $2B budget to implement a strategy under NAPA.

If we are to wage a war against this disease, then research funds to better understand Alzheimer's and to develop a cure must be the center-piece of the strategy. However, I hope that the planners do not overlook more certain, and more immediate opportunities to win many battles. Great progress can be achieved with not much more than a dose of pragmatism and public will. I described those opportunities in some detail in an earlier post "Antidote for the Alzheimer's Epidemic".

Given the fast pace of research in this field over the past decade, coupled with historically slow adoption of new knowledge into clinical practice, there is a large gap between the state of our medical knowledge and the standards of care we commonly practice in the clinic.

So let's commit to a national plan for thwarting Alzheimer's and focus on developing a cure. But let's make sure we also take care to update clinical practice with all of the new discoveries we have made, and will continue to make, as we race toward that ultimate goal.

Dimebon, an experimental Alzheimer's treatment, has failed its Phase III clinical trial, and will not be further developed by its co-sponsors, Pfizer and Medivation.

The Associated Press article reporting on this failure described it as a "major setback" but it really comes as no surprise to those who have followed the trajectory of this potential new drug.

As we described in an earlier post, Dimebon failed its initial trial showing no cognitive benefits and no improvement of function among those research subjects who took it. Undaunted by the initial failure, the drug's sponsors pushed forward with three additional trials: one measuring the drug's effect over a longer period, one measuring the drug's effect as poly-therapy in conjunction with Aricept, and one measuring the drug's effect in patients with Huntington's disease. All three trials have now failed.

This is not good news for the field but I think it important to comment on how this might effect attitudes toward further research. By and large, even the first Dimebon failure in March of 2010 was expected by most experts who follow this space. Despite the fact that Pfizer and Medivation chose to push forward and complete three additional studies, consensus was that the drug was unlikely to be effective, and success in those trials was considered an absolute long-shot.

Now, those expectations have been met, and no one is really surprised. Research will continue at a cautious but steady pace, perpetually fueled by the lucrative potential of success.

According to the Center for Disease Control and Prevention, longevity has ticked up in America with life expectancy climbing to almost 79 years.

Homicide and cancer, two prominent causes of death, both declined in the past year and contributed to longer lives across the American population. This is good news overall, but belies a trend that will continue to redefine which risks and priorities demand our national focus.

An obvious implication of a longer life span is that medical conditions correlated with aging will become more prevalent. This portends a rising incidence of Alzheimer's disease as a higher percentage of the population lives will into the years when they are most at risk for that terrible disease.

We all want to live longer, healthier lives and the general trend suggests that each of us enjoys a rising likelihood that we will do so. But as we all traverse the lengthening arc of our elder years, we must face a shifting set of threats to our livelihood. In today's reality, one of the key risks we must prepare to manage in the final years of our projected lives, is the risk of dementia caused by Alzheimer's disease.

Fortunately, a vast research effort is underway to identify manageable risks for AD and to develop guidelines for minimizing the likelihood of suffering its consequences. We review that research on a regular basis in this blog and strive to keep our audience abreast of the latest developments in this important field.

It's been a long time coming, but the FDA might finally have enough evidence to allow bio-marker measures into clinical trials for Alzheimer's treatments. This change could potentially speed the trial process, reduce the risk of failed trials, and yield new AD therapies in the near future.

Based on an analysis of prior publications about bio-markers for Alzheimer's disease, an expert panel convened by the Alliance for Aging Research and the FDA, found ample scientific evidence for including changes in bio-markers as outcome measures in FDA clinical trials. This means that, rather than relying solely on measures of cognition and function (which are measures of worsening symptoms), a drug could now be approved based on its ability to prevent pathological changes that are only evident through an examination of bio-marker measures.

An obvious precedent for this approach comes from the cholesterol field. Since high cholesterol is a condition with no immediately apparent symptoms, a trial based on symptomatic improvement would always fail. To approve cholesterol reducing drugs, the FDA allowed trial designs that used blood-based measures of cholesterol as a bio-marker, in lieu of any symptoms produced by a high cholesterol level.

It has long been known that Alzheimer's disease is characterized by a series of pathological changes. These changes progress from shifting protein levels in the spinal fluid, then to lesions in the brain, and eventually to brain atrophy. However, the precise relationship between the disease and these pathological changes had not been well enough understood for the FDA to allow their measures as part of a clinical trial. With a massive research focus over the past five years and what appears to be an objective, expert review of the evidence, it appears as though future trials may well include bio-marker measures as critical trial outcomes.

Many Alzheimer's related stories get massive press coverage, despite minimal importance in the grand scheme of our efforts to thwart the disease. This story has been relatively uncovered in the mainstream, but might well be one of the most important stories of the year.